The pharmacological actions of neuropeptides in the central nervous system are studied to determine possible physiological or pathophysiological actions of the peptide and the therapeutic potential of a neuropeptide super-agonist or antagonist. A number of neuropeptide systems are thought to interact with dopaminergic systems in the brain. Because of the clinical relevance of dopaminergic systems to neurological disorders, the pharmacology of these systems which contain and secrete substance P (SP), neurotensin (NT), secretin (SEC) and bomesin (BN) were explored. Receptor assays or radioimmunoassays for each of the peptides were developed by radiolabelling the peptides with iodine or tritium. The distribution of receptors was determined using autoradiographic methods. SP is found in high concentrations in the striatum and the substantia nigra. Consistently, high densities of SP receptors were found in the striatum but surprisingly, few if any receptors were found in the substantia nigra. It therefore appears that SP modulation of the nigrostriatal dopaminergic system must occur at the level of the striatum. Structure-activity studies of SP indicate that carboxy-terminus contains the critical sequence of amino acids required for receptor recognition. Unlike SP, it was found that NT has receptors both on perikarya and terminals of the nigrostriatal dopaminergic system. In addition, NT receptors were found on dopaminergic terminals inthe nucleus accumbens. Similarly, BN receptors were found in high density in the striatum and particularly high density in the nucleus accumbens. The laboratory has recently identified SEC in the brain. An injection of SEC into the lateral ventricle of a conscious rat causes motor changes which include a decrease in open-field locomotor activity which can be reversed by administration of haloperidol, a dopaminergic antagonist. SEC receptors were identified in the rat brain and structure activity studies showed that essentially the whole SEC sequence of 27 amino acids is required for receptor binding.